TY - JOUR
T1 - Association of metformin administration with gut microbiome dysbiosis in healthy volunteers
AU - Elbere, Ilze
AU - Kalnina, Ineta
AU - Silamikelis, Ivars
AU - Konrade, Ilze
AU - Zaharenko, Linda
AU - Sekace, Kristine
AU - Radovica-Spalvina, Ilze
AU - Fridmanis, Davids
AU - Gudra, Dita
AU - Pirags, Valdis
AU - Klovins, Janis
N1 - Publisher Copyright:
© 2018 Elbere et al.
PY - 2018/9
Y1 - 2018/9
N2 - Background Metformin is a widely used first-line drug for treatment of type 2 diabetes. Despite its advantages, metformin has variable therapeutic effects, contraindications, and side effects. Here, for the very first time, we investigate the short-term effect of metformin on the composition of healthy human gut microbiota. Methods We used an exploratory longitudinal study design in which the first sample from an individual was the control for further samples. Eighteen healthy individuals were treated with metformin (2 × 850 mg) for 7 days. Stool samples were collected at three time points: Prior to administration, 24 hours and 7 days after metformin administration. Taxonomic composition of the gut microbiome was analyzed by massive parallel sequencing of 16S rRNA gene (V3 region). Results There was a significant reduction of inner diversity of gut microbiota observed already 24 hours after metformin administration. We observed an association between the severity of gastrointestinal side effects and the increase in relative abundance of common gut opportunistic pathogen Escherichia-Shigella spp. One week long treatment with metformin was associated with a significant decrease in the families Peptostreptococcaceae and Clostridiaceae 1 and four genera within these families. Conclusions Our results are in line with previous findings on the capability of metformin to influence gut microbiota. However, for the first time we provide evidence that metformin has an immediate effect on the gut microbiome in humans. It is likely that this effect results from the increase in abundance of opportunistic pathogens and further triggers the occurrence of side effects associated with the observed dysbiosis. An additional randomized controlled trial would be required in order to reach definitive conclusions, as this is an exploratory study without a placebo control arm. Our findings may be further used to create approaches that improve the tolerability of metformin.
AB - Background Metformin is a widely used first-line drug for treatment of type 2 diabetes. Despite its advantages, metformin has variable therapeutic effects, contraindications, and side effects. Here, for the very first time, we investigate the short-term effect of metformin on the composition of healthy human gut microbiota. Methods We used an exploratory longitudinal study design in which the first sample from an individual was the control for further samples. Eighteen healthy individuals were treated with metformin (2 × 850 mg) for 7 days. Stool samples were collected at three time points: Prior to administration, 24 hours and 7 days after metformin administration. Taxonomic composition of the gut microbiome was analyzed by massive parallel sequencing of 16S rRNA gene (V3 region). Results There was a significant reduction of inner diversity of gut microbiota observed already 24 hours after metformin administration. We observed an association between the severity of gastrointestinal side effects and the increase in relative abundance of common gut opportunistic pathogen Escherichia-Shigella spp. One week long treatment with metformin was associated with a significant decrease in the families Peptostreptococcaceae and Clostridiaceae 1 and four genera within these families. Conclusions Our results are in line with previous findings on the capability of metformin to influence gut microbiota. However, for the first time we provide evidence that metformin has an immediate effect on the gut microbiome in humans. It is likely that this effect results from the increase in abundance of opportunistic pathogens and further triggers the occurrence of side effects associated with the observed dysbiosis. An additional randomized controlled trial would be required in order to reach definitive conclusions, as this is an exploratory study without a placebo control arm. Our findings may be further used to create approaches that improve the tolerability of metformin.
UR - http://www.scopus.com/inward/record.url?scp=85054101201&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0204317
DO - 10.1371/journal.pone.0204317
M3 - Article
C2 - 30261008
AN - SCOPUS:85054101201
SN - 1932-6203
VL - 13
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e0204317
ER -